A randomized, placebo-controlled, trial to assess the photosensitizing, phototoxic and carcinogenic potential of hydrochlorothiazide in healthy volunteers

Abstract

Background and aims: Pharmacovigilance reports, associating hydrochlorothiazide (HCT) with skin cancer, resulted in a significant decrease of HCT prescriptions for hypertension and heart failure. Whether HCT exhibits phototoxic properties thereby causing skin cancer remains unknown. This study aimed to examine the photosensitizing, phototoxic and carcinogenic potential of HCT in a randomized, placebo-controlled, double-blind trial in vivo and also in vitro. Methods: The trial assigned 30 healthy, normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg/day or placebo for 15 days. Photosensitivity of the skin with and without the effect of HCT treatment were assessed. Following whole-body ultraviolet A (UVA) and B (UVB, 311 nm) irradiation, phototoxic and carcinogenic reactions by measuring urinary excretion of pyrimidine dimers were evaluated. For the in-vitro studies, human keratinocytes (HaCaT) were incubated with HCT, irradiated with UVB, and analysed for markers of inflammation, apoptosis and carcinogenesis. Results: Skin photosensitivity following exposure to UVA and UVB remained unchanged from baseline to 15-day follow-up in both groups (UVA change HCT 0.0 J/cm2 vs. placebo 0.0 J/cm2; P = 0.99; UVB change HCT 0.0 J/cm2 vs. placebo -0.2 J/cm2; P = 0.06). Pyrimidine dimers were not detected in either group. In vitro, combination of HCT and UVB irradiation did not induce the expression of oxidative stress marker proteins, inflammatory proteins, apoptotic proteins or activation of oncoproteins. Conclusion: HCT did not increase photosensitivity for UVA or UVB in healthy volunteers compared with placebo, and was not associated with phototoxic or carcinogenic reactions. In vitro, HCT was also not associated with phototoxicity or carcinogenesis (NCT04654312).

Prescription Trends of Thiazide Diuretics in a Canadian Primary Care Population From 2015 to 2021

“… 26 Another recently published, small, randomized, placebo-controlled trial concluded that HCTZ did not increase photosensitivity and was not associated with phototoxic or carcinogenic reactions. 27 More research is needed given the heterogeneous conclusions of previous studies.…”

Hydrochlorothiazid: Erhöhtes Risiko für atypisches Fibroxanthom und pleomorphes dermales Sarkom

“…27 UVA-Strahlung dringt bis in die Dermis vor und interagiert dort mit Fibroblasten. 45 46 Darüber hinaus bestätigt die vorliegende Studie die epidemiologischen Daten für AFX/PDS mit einer starken männlichen Dominanz (88,9% Männer) und überwiegend betroffenen älteren Patienten, wobei 84,5% der AFX/PDS-Diagnosen bei Patienten über 75 Jahren gestellt wurden (Tabelle 1). 6,11 Zusätzlich stehen die vorliegenden Daten im Einklang mit früheren Erkenntnissen, dass die Diagnose eines AFX/PDS mit weiteren NMSC assoziiert ist, da 54,1% der AFX/PDS-Patienten mindestens ein weiteres vorbekanntes NMSC aufwiesen.…”

Phototoxic and carcinogenic effects of hydroclorothiazide: experimental study contrasting the pharmacoepidemiological evidence showing increased risk of skin cancer

“…In this issue of the Journal, an experimental study of the phototoxic and carcinogenic potential of HCT is reported [9]. The authors studied 30 healthy individuals.…”